Purpose: Sipuleucel-T, an autologous cellular immunotherapy, was investigated in a randomized, double-blind, controlled trial to determine its biologic activity in androgen-dependent prostate cancer (ADPC).Experimental Design: Patients with prostate cancer detectable by serum prostate-specific antigen (PSA) following radical prostatectomy received 3 to 4 months of androgen suppression therapy, and were then randomized (2:1) to receive sipuleucel-T (n ¼ 117) or control (n ¼ 59). The primary endpoint was time to biochemical failure (BF) defined as serum PSA 3.0 ng/mL. PSA doubling time (PSADT), time to distant failure, immune response, and safety were also evaluated.Results: Median time to BF was 18.0 months for sipuleucel-T and 15.4 months for control (HR ¼ 0.936, P ¼ 0.737). Sipuleucel-T patients had a 48% increase in PSADT following testosterone recovery (155 vs. 105 days, P ¼ 0.038). With only 16% of patients having developed distant failure, the treatment effect favored sipuleucel-T (HR ¼ 0.728, P ¼ 0.421). The most frequent adverse events in sipuleucel-T patients were fatigue, chills, and pyrexia. Immune responses to the immunizing antigen were greater in sipuleucel-T patients at Weeks 4 and 13 (P < 0.001, all) and were sustained prior to boosting as measured in a subset of patients a median of 22.6 months (range: 14.3-67.3 months) following randomization.Conclusions: No significant difference in time to BF could be shown. The finding of increased PSADT in the sipuleucel-T arm is consistent with its biologic activity in ADPC. Long-term follow-up will be necessary to determine if clinically important events, such as distant failure, are affected by therapy. Treatment was generally well tolerated. Clin Cancer Res; 17(13); 4558-67. Ó2011 AACR.

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